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expert reaction to a Wellcome announcement on a new Synthetic Human Genome research project (SynHG)

Experts comment on a new research project that aims to synthesise human genomes announced by Wellcome. 

 

Prof Robin Lovell-Badge FRS FMedSci, Group Leader, Francis Crick Institute, said:

“Despite all the knowledge gained from sequencing (reading) human genomes, which began with the first about 25 years ago and has been rapidly accelerating ever since, there is a lot we do not understand about how they work. The protein encoding parts are fairly straightforward, but these comprise only a small fraction of the total. There are segments, notably those that contain highly repetitive DNA at the ends of chromosomes (telomeres) and the centromeres that play a role in segregating the chromosomes to each daughter cell when it divides, about which we know less. There are also huge numbers of repetitive elements, some remnants of viruses that have integrated into the genome or have been copied and moved around. Each gene also has a regulatory region that controls when and where it will be expressed (active) within cells. Some of these elements and the proteins with which they interact are also responsible for dynamic folding and generally organising the genome, which in turn is thought to help not just tight packaging of the chromosomes when the cell divides but also efficient control of gene activity. We can test the role of some of these elements, but given that many may be superfluous or even just evolutionary relics with no clear function (‘junk’ DNA), this is time consuming, expensive and often not rewarding. Being able to build and redesign segments or entire human chromosomes will be important – after all you can only truly understand something if you can build it from scratch. And if you understand what is relevant and important, it may be possible to refine or improve aspects of its activity – for example to more efficiently express gene products of medical value – or redesign it to make novel gene products.

“I am therefore very enthusiastic about the project being launched by Wellcome, but not just about the scientific possibilities. It is critical when developing new technology to understand not just issues of potential utility, but also those concerned with safety and risk and very importantly the societal values on which it may impinge. Maintaining an active dialogue with varied publics will be important to help build in barriers where needed and to develop appropriate regulation to permit safe practices. It is also required to identify and understand hopes and concerns, where to draw limits and what other, even unrelated factors might influence where the science should be allowed to go. This is important in order to judge where the research needs particularly tight scrutiny and to define under what conditions even some experiments deemed to be of high risk might proceed or whether they should be prohibited outright for being far too dangerous. The latter is the recommendation for building ‘mirror life’ (organisms where all their DNA and proteins have the opposite chirality or twist.

“As for synthetic human chromosomes, although the current project is very unlikely to get that far, it may eventually be possible to make synthetic cells that can be grown in the lab with high efficiency. If these were to ever be used in humans, it would be important to design them carefully so that they can’t lead to tumours or produce novel infectious particles. Indeed, I would urge incorporating an inducible genetic kill switch to eliminate them from any location in the body or at least to make them easy for the immune system find and destroy. However, there is no suggestion to make synthetic humans. We have no idea how to do this and it is likely to be very unsafe.”

 

Sarah Norcross, Director of the Progress Educational Trust (PET), said:

“It’s incredibly exciting to see such a wide-ranging project announced that will focus on human genome synthesis. Synthesising human genomes is a logical next step after what has been achieved to date with sequencing and editing human genomes, and this is also work that can benefit from current advances in AI. We sometimes forget that generative AI encompasses not just the generation of text, images and sounds, but also the generation of possible molecules that might then be synthesised in the laboratory.

“There are two important nuances to add. First, we must recognise that this sort of work is not without controversy, and that is vital for researchers and the public to be in communication with one another. The public must have a clear understanding of what this research entails, while researchers and funders must have a thoroughgoing understanding of where the public wants to go with this science. We are therefore extremely pleased to see that a dedicated social science programme has been incorporated into this work at the outset, headed by Professor Joy Zhang.

“Second, we must not forget ongoing work in genome sequencing and genome editing, which remains vital. Although the Human Genome Project was ostensibly completed in 2003, the human genome was not actually sequenced in its entirety until the Telomere to Telomere Consortium concluded its work 20 years later. As for human genome editing, we have barely begun to explore the possibilities and consequences of that technology, and we have seen one appalling (and thankfully isolated) instance of its misuse.

“All of these different ways of investigating and working with human genomes must be approached with diligence, with a balance between ambition and humility, and with a view to public interests and concerns.”

 

 

 

* https://www.bbc.co.uk/news/articles/c6256wpn97ro

* Wellcome press release: https://wellcome.org/news/new-project-pioneer-principles-human-genome-synthesis

 

 

 

Declared interests

Sarah Norcross: PET is a charity which improves choices for people affected by infertility and genetic conditions.”

For all other experts, no reply to our request for DOIs was received.

 

 

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